The overall objective of this research is to elucidate the cellular and molecular processes involved in the biosynthesis and assembly of several hepatically derived plasma proteins. Fibrinogen, the blood clotting protein; haptoglobin binding protein; ceruloplasmin, the copper binding protein; and the C-reactive protein are the major hepatic constituents we are studying. Fibrinogen and haptoglobin are of particular interest because they are multichained proteins and the mode of subunit assembly to provide a functional molecule is currently unknown. We are currently attempting to isolate the mRNA's for each of the protein subunits and investigate their mode of assembly in the cell free synthesizing system. Another aspect of the study has been to develop a liver cell culture system that synthesizes the proteins we are studying. We have succeeded in establishing a primary culture that synthesizes fibrinogen, haptoglobin and albumin. The hepatocyte culture also has the capability of being stimulated to increase its synthesis of these proteins by factors derived from polymorphonuclear leucocytes. We are investigating not only the chemical nature of the inducing molecule but also attempting to elucidate precisely how it brings about the stimulation of synthesis of these plasma proteins. Because of the critical importance of these selected plasma proteins in maintaining body function, a thorough knowledge of the cellular and molecular mechanisms of their biosynthesis is essential.